Lancet
2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.
Salah-Eddin Al-Batran 1, Nils Homann 2, Claudia Pauligk 3, Thorsten O Goetze 3, Johannes Meiler 4, Stefan Kasper 4, Hans-Georg Kopp 5, Frank Mayer 6, Georg Martin Haag 7, Kim Luley 8, Udo Lindig 9, Wolff Schmiegel 10, Michael Pohl 11, Jan Stoehlmacher 12, Gunnar Folprecht 12, Stephan Probst 13, Nicole Prasnikar 14, Wolfgang Fischbach 15, Rolf Mahlberg 16, Jörg Trojan 17, Michael Koenigsmann 18, Uwe M Martens 19, Peter Thuss-Patience 20, Matthias Egger 21, Andreas Block 22, Volker Heinemann 23, Gerald Illerhaus 24, Markus Moehler 25, Michael Schenk 26, Frank Kullmann 27, Dirk M Behringer 28, Michael Heike 29, Daniel Pink 30, Christian Teschendorf 31, Carmen Löhr 32, Helga Bernhard 33, Gunter Schuch 34, Volker Rethwisch 29, Ludwig Fischer von Weikersthal 35, Jörg T Hartmann 36, Michael Kneba 37, Severin Daum 38, Karsten Schulmann 39, Jörg Weniger 40, Sebastian Belle 41, Timo Gaiser 42, Fuat S Oduncu 43, Martina Güntner 44, Wael Hozaeel 45, Alexander Reichart 46, Elke Jäger 46, Thomas Kraus 47, Stefan Mönig 48, Wolf O Bechstein 49, Martin Schuler 50, Harald Schmalenberg 51, Ralf D Hofheinz 52; FLOT4-AIO Investigators
Affiliations Expand
PMID: 30982686
Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.
Methods: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644.
Findings: Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group.
Interpretation: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX.